Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

2021 ◽  
Author(s):  
Wooram Park ◽  
Seok-Jo Kim ◽  
Paul Cheresh ◽  
Jeanho Yun ◽  
Byeongdu Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cancer Cell ◽  
High Sensitivity ◽  
Intrinsic Pathway ◽  
Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

Modulating autophagy in cancer therapy: Advancements and challenges for cancer cell death sensitization

2018 ◽  
Vol 147 ◽  
pp. 170-182 ◽  
Author(s):  
Punya Bhat ◽  
Jurgen Kriel ◽  
Babu Shubha Priya ◽  
Basappa ◽  
Nanjunda Swamy Shivananju ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cell ◽  
Cancer Cell Death

scholarly journals Selective imaging and cancer cell death via pH switchable near-infrared fluorescence and photothermal effects

2016 ◽  
Vol 7 (9) ◽  
pp. 5995-6005 ◽  
Author(s):  
Jingye Zhang ◽  
Zining Liu ◽  
Peng Lian ◽  
Jun Qian ◽  
Xinwei Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Near Infrared ◽  
Near Infrared Fluorescence ◽  
Ph Changes ◽  
Cancer Cell Death ◽  
Photothermal Effects

A theranostic probe is designed that specifically illuminates and photoablates cancer cells by sensing pH changes in the lysosomes and mitochondria.

scholarly journals Mitochondrial Complex I Inhibitors and Forced Oxidative Phosphorylation Synergize in Inducing Cancer Cell Death

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Roberta Palorini ◽  
Tiziana Simonetto ◽  
Claudia Cirulli ◽  
Ferdinando Chiaradonna
Keyword(s):  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Low Doses ◽  
Mitochondrial Complex ◽  
Cancer Cell Death ◽  
Glucose Depletion

Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS) for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.

scholarly journals Cold Physical Plasma in Cancer Therapy: Mechanisms, Signaling, and Immunity

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Fatemeh Faramarzi ◽  
Parisa Zafari ◽  
Mina Alimohammadi ◽  
Mohammadreza Moonesi ◽  
Alireza Rafiei ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Plasma Treatment ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Intracellular Signaling ◽  
Current Knowledge ◽  
Cancer Cell Death ◽  
Physical Plasma

Despite recent advances in therapy, cancer still is a devastating and life-threatening disease, motivating novel research lines in oncology. Cold physical plasma, a partially ionized gas, is a new modality in cancer research. Physical plasma produces various physicochemical factors, primarily reactive oxygen and nitrogen species (ROS/RNS), causing cancer cell death when supplied at supraphysiological concentrations. This review outlines the biomedical consequences of plasma treatment in experimental cancer therapy, including cell death modalities. It also summarizes current knowledge on intracellular signaling pathways triggered by plasma treatment to induce cancer cell death. Besides the inactivation of tumor cells, an equally important aspect is the inflammatory context in which cell death occurs to suppress or promote the responses of immune cells. This is mainly governed by the release of damage-associated molecular patterns (DAMPs) to provoke immunogenic cancer cell death (ICD) that, in turn, activates cells of the innate immune system to promote adaptive antitumor immunity. The pivotal role of the immune system in cancer treatment, in general, is highlighted by many clinical trials and success stories on using checkpoint immunotherapy. Hence, the potential of plasma treatment to induce ICD in tumor cells to promote immunity targeting cancer lesions systemically is also discussed.

scholarly journals Targeted Depletion of Amino Acids As a Novel Therapy for Acute Leukemia and Other Cancers: Mechanisms and Countermechanisms

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4716-4716 ◽  
Author(s):  
Aysenur Esen ◽  
Anwar A Khan ◽  
Jason Chan ◽  
Nadim Mahmud ◽  
John G. Quigley
Keyword(s):  
Amino Acids ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stress Responses ◽  
Drug Combination ◽  
Metabolic Reprogramming ◽  
Low Doses ◽  
Cancer Cell Death ◽  
Mtorc1 Pathway

Abstract Introduction: Metabolic reprogramming by cancer cells to allow proliferation and survival suggests targeting of relatively cancer cell-specific metabolic processes as a potential cancer therapy. The amino acid (aa) glutamine (GLN) functions as an exchange factor to facilitate cell import of essential amino acids (EAA), which positively regulate translation by the mTORC1 pathway (via phosphorylation of S70K and 4EBP1), allowing proliferation. Most cancer cells also rely on GLN, rather than glucose for citric acid cycle (TCA) anaplerosis, and as a source of energy, anti-oxidants and components for protein synthesis. L-asparaginase (L-Ase), an enzyme that breaks down extracellular asparagine (ASN, the least prevalent intracellular aa), is used in the treatment of ALL. L-Ase is also glutaminolytic, resulting in GLN depletion and apoptosis that is suppressed by ASN repletion, which modulates the cell stress responses (ISR, upregulatingATF4, CHOP, aa transporters, and asparagine synthetase (ASNS)). Thus, (i) ASN is a critical signal preventing cell death from GLN depletion; (ii) ASN repletion (via ASNS) may be the important function of GLN within cancer cells, and (iii) mechanisms that deplete bothkey aa may be synergistic in implementing cancer cell death Apart from non-EAA synthesis and aa uptake (#1 in Fig. 1A), there are two major pathways of cellular aa repletion: (i) autophagy, a process whereby damaged proteins are delivered to the lysosome for degradation (#2), and (ii) the ubiquitin-proteasome system (UPS, #3), which also degrades damaged or misfolded cell proteins, allowing aa recycling. Notably, UPS inhibition significantly decreases ASN (andcystine) levels. The aim of our studies is to explore mechanisms of depleting intracellular GLN and ASN levels in cancer cells, firstinvestigating the potential synergistic effects of combining L-Ase, with Chloroquine (CQ, autophagy inhibition) and Bortezomib (BTZ, proteasome inhibition), and then analyzing cancer cell counter mechanisms. Results: We performed kill-curves with individual drugs, and then combinations of L-ase, CQ and BTZ in REH (ALL) cells. Notably, inhibitory effects on aarepletion pathways, as determined by western blot analysis of cell lysates at 12h (Fig. 1B), were seen with a combination of significantly lowered doses of each drug [BTZ 2nM (40% of LD50); L-Ase 0.2IU (15%); CQ 100mM (50%)]. The mTORC1 pathway is especially susceptible to inhibition by drug combination-mediated aa depletion (decreased phosphorylation of 4EBP1 and S6K1; compare lanes 2-4 & 5-8), while autophagy (monitored by increasing levels of LC3-II) is also inhibited. Cell viability was assessed after 48h. Although the low doses of each drug used has a minimal impact on viability (range 75-130% of control), the combination above (2nM;0.2IU;100mM) results in synergistic cell death [55% (n = 1)]. We will examine further the effects of this drug combination on normal CD34+ cells, prior to studies of efficacy inxeno-transplant models. Most tumors are metabolically flexible, e.g., they can use glucose if deprived of GLN to replenish TCA, and, via TCA intermediates, increase GLN levels, and thereby ASN, via pyruvate carboxylase (PC), transaminases (GOT1, 2), glutaminesynthetases(GDH, GS) and ASNS (see Fig. 1 pathways). Thus, we interrogated, byqPCR, potentially relevant pathways that may be used to evade glutamine and asparagine depletion-induced apoptosis (Fig. 1C). Of 12 genes tested, GLN deprivation significantlyupregulatesGLS1, GOT1, and ASNS to increase ASN levels, while the ISR is activated (CHOP), and SLC7A11, a cysteine importer upregulated in tumors (for glutathione production) is also significantly upregulated. Preliminary studies of REH and A549 (lung cancer) cells suggest a common theme in metabolic responses to GLN depletion in diverse cancer cells is ASN synthesis through GOT1 and ASNS upregulation, and likely ROS production throughcystineuptake. Conclusions: Commonly, inhibition of one metabolic pathway results in upregulation of another. Our studies indicate that combination therapy, using low doses of available, well-studied drugs depletes keyaa ASN and GLN, and prevents their repletion, causing cancer cell death. In addition, our studies of the cellular responses to GLN depletion alone indicate additional targets that should be considered to prevent ASN-mediated inhibition of cell death in diverse cancer types. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Fluorinated thiazolidinols cause cell death in A549 lung cancer cells via PI3K/AKT/mTOR and MAPK/ERK signalling pathways

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1197-1203 ◽  
Author(s):  
Ravindra M. Kumbhare ◽  
Tulshiram L. Dadmal ◽  
Dinesh Kumar ◽  
M. Janaki Ramaiah ◽  
Anudeep Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Signalling Pathways ◽  
Lung Cancer Cell ◽  
Cancer Cell Death ◽  
A549 Lung Cancer Cell ◽  
A549 Lung

Fluorinated thiazolidinols cause A549 lung cancer cell death by acting via PI3K/Akt/mTOR and MEK/ERK pathways.

New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways

2016 ◽  
Vol 45 (22) ◽  
pp. 9345-9353 ◽  
Author(s):  
Asfa Ali ◽  
Mohini Kamra ◽  
Arunoday Bhan ◽  
Subhrangsu S. Mandal ◽  
Santanu Bhattacharya
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Metal Complexes ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Salen Complexes ◽  
Selective Targeting

Distamycin like moieties conjugated with core Fe(iii) and Co(ii) based salens were synthesized and studied. The metal complexes showed better and differential activity toward cancer cell death.

Tripeptide consisting of benzyl protected di-cysteine and phenylalanine forms spherical assembly and induces cytotoxicity in cancer cells via apoptosis

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112667-112676 ◽  
Author(s):  
Biswadip Banerji ◽  
Moumita Chatterjee ◽  
Chandraday Prodhan ◽  
Keya Chaudhuri
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Growth Medium ◽  
Cancer Cell Death

Tripeptide self assemblies in cell growth medium induce apoptosis and promoting cancer cell death at submicromolar concentration.

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